1-(1,2-DISUBSTITUTED PIPERIDINYL)-4-SUBSTITUTED PIPERIDINE DERIVATIVES AS TACHYKININ RECEPTOR ANTAGONISTS

摘要

The present invention concerns compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein n is 0, 1 or 2; m is 1 or 2, provided that if m is 2, then n is 1; p is 0, 1 or 2; =Q is =O or =NR<3>; X is a covalent bond or a bivalent radical of formula -O-, -S-, -NR<3>-; R<1> is Ar<1>; Ar<1>C1-6alkyl or di(Ar<1>)C1-6alkyl, wherein each C1-6alkyl group is optionally substituted with hydroxy, C1-4alkyloxy, oxo or a ketalized oxo substituent of formula -O-CH2-CH2-O- or -O-CH2-CH2-CH2-O-; R<2> is Ar<2>; Ar<2>C1-6alkyl; Het or HetC1-6alkyl; R<3> is hydrogen or C1-6alkyl; R<4> is hydrogen; C1-4alkyl; C1-4alkyloxyC1-4alkyl; hydroxyC1-4alkyl; carboxyl; C1-4alkyloxycarbonyl or Ar<3>; R<5> is hydrogen; hydroxy; Ar<3>; Ar<3>C1-6alkyloxy; di(Ar<3>)C1-6alkyloxy; Ar<3>C1-6alkylthio; di(Ar<3>)C1-6alkylthio; Ar<3>C1-6alkylsulfoxy; di(Ar<3>)C1-6alkylsulfoxy; Ar<3>C1-6alkylsulfonyl; di(Ar<3>)C1-6alkylsufonyl; -NR<7>R<8>; C1-6alkyl substituted with -NR<7>R<8>; or a radical of formula (a-1) or (a-2); R<4> and R<5> may also be taken together; R<6> is hydrogen; hydroxy; C1-6alkyloxy; C1-6alkyl or Ar<3>C1-6alkyl; Ar<1>, Ar<2> and Ar<3> are phenyl or substituted phenyl; Ar<2> is also naphthalenyl; and Het is an optionally substituted monocyclic or bicyclic heterocycle; as substance P antagonists; their preparation, compositions containing them and their use as a medecine.